Each year approximately 310,000 Americans die of sudden cardiac death (SCD) from ventricular tachyarrhythmias [Lloyd-Jones 2009]. The first preventive step toward reducing mortality from SCD is to identify individuals at risk for developing arrhythmias. Yet, despite years of research, the risk stratification strategies are unclear and there are still no reliable clinical tests that predict who is susceptible to this potentially lethal heart rhythm disorders [Kusmirek & Gold 2007].
Currently, the most reliable method of assessing vulnerability to cardiac arrhythmias is EP testing, in which a provocative intracardiac pacing protocol is applied to the patient with an aim of inducing an arrhythmia episode [Daubert 2006]. EP testing is an invasive procedure and carries a non-negligible risk of death. In contrast, the present invention can evaluate stability-of-propagation reserve (SoPR) from data collected either invasively or noninvasively. Even if invasive data collection is used, the pacing protocol for determination of the SoPR is significantly less aggressive and provocative than standard intracardiac arrhythmia inducibility protocols. Thus, the risk to the patient is well below the risk of current EP testing.
Of the noninvasive methods, the most successful is the T-wave alternans (TWA) testing [Hayhjoo 2006], which detects a low-amplitude beat-to-beat fluctuation of the ECG T-wave. TWA reflects cellular alternans, i.e., long-short alternation in action potential duration (APD). Theory of excitable media and nonlinear dynamics predict that APD alternans can result in a unidirectional conduction block, reentry, and the onset of a tachyarrhythmia [Myles 2008]. However, alternans is only one possible route to a fatal arrhythmia (FIG. 1). Conduction blocks can occur without prior alternans. For example, unidirectional conduction block may occur in response to a premature stimulus applied to the tissue with a critical level of refractoriness, or wave-break and conduction block may occur when there is interaction with a less excitable portion of cardiac tissue [Starobin 1996, Fenton 2002].
Because TWA predicts just one of possible precursors of arrhythmia, it works well only in a limited group of the highest-risk patients with a history of sustained ventricular arrhythmias [Kismirek & Gold 2007]. In contrast, the present invention predicts the likelihood of conduction block, not just one of its precursors. Therefore, it should capture a wider range of proarrhythmic states and work in a broader population of patients at risk. In addition, the present invention can be implemented using current commercial ECG exercise testing equipment, while TWA testing requires special instrumentation to detect microvolt-level alternans.